Abstract
Abstract The tumor suppressor p53 is mutated in approximately 30% of breast adenocarcinomas, but the clinical implications of p53 mutation depend on the subtype of breast tumor. Although p53 mutation is associated with worse outcome for patients with Luminal B and Her2 subtypes, the same is not true in Basal tumors, despite the fact that Basal tumors have the highest frequency of p53 mutation of any subtype. Lymphocytic infiltration is associated with better prognosis in several epithelial malignancies including triple-negative breast tumors. In this study we identify an association in Basal breast cancer between lymphocytic infiltration and the number of copies of wild-type p53 by combining gene expression, p53 sequencing, DNA copy number analysis, and semi-quantitative immune cell histology in 1,281 tumors. We use the Nanodissect algorithm to define signatures for T cell types and show that the infiltration consists primarily of cytotoxic T lymphocytes. Elevated expression of this gene signature is associated with better outcome in Basal tumors, and differential pathway activity analysis identifies significant activation of caveolin 1 signaling to TGF-beta in p53 wild-type Basal tumors. These findings identify a new link between the p53 pathway and beneficial adaptive immune response in breast tumors not responsive to the estrogen receptor, supporting a connection between a lack of p53 function and the failure of tumor immunosurveillance. This abstract is also presented as Poster A35. Citation Format: David A. Quigley, Charlie Vaske, Laxmi Silwa-Pandit, Ruth Dannenfelser, Anita Langerød, Hans Kristian M. Vollan, Olga Troyanskaya, Suet-Feung Chin, Carlos Caldas, Allan Balmain, Anne-Lise Børresen-Dale, Vessela Kristensen. Lymphocyte invasion of basal breast tumors is associated with wild-type p53. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR06. doi:10.1158/1538-7445.CHTME14-PR06
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